Epigenetic therapy attenuates oxidative stress in BMSCs during ageing.

ABSTRACT: Oxidative stress, a hallmark of ageing, inhibits the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in long bone. The dysfunction of the cellular antioxidant defence system is a critical cause of oxidative stress, but the mechanism of the decline of antioxidant defence in senescent stem cells remains elusive. Here, we found that EZH2, an epigenetic regulator of histone methylation, acted as a suppressor of the antioxidative defence system in BMSCs from the femur. The increased EZH2 led to a decrease in the levels of antioxidant enzymes and exaggerated oxidative damage in aged BMSCs, resulting in the defect of bone formation and regeneration. Mechanistically, EZH2 enhanced the modification of H3K27me3 on the promoter of Foxo1 and suppressed its function to activate

SUBMITTER: Su X 

PROVIDER: S-EPMC8743666 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature